Toll-Like Receptors and Dectin-1, a C-Type Lectin Receptor, Trigger Divergent Functions in CNS Macrophages

Spinal cord injury (SCI) activates macrophages, endowing them with both reparative and pathological functions. The mechanisms responsible for these divergent functions are unknown but are likely controlled through stochastic activation of different macrophage receptor subtypes. Various danger-associated molecular patterns released from dying cells in the injured spinal cord likely activate distinct subtypes of macrophage pattern recognition receptors, including bacterial toll-like receptors (TLRs) and fungal C-type lectin receptors (e.g., dectin-1). To determine the in vivo consequences of activating these receptors, ligands specific for TLR2 or dectin-1 were microinjected, alone or in combination, into intact spinal cord. Both ligands elicit a florid macrophage reaction; however, only dectin-1 activation causes macrophage-mediated demyelination and axonal injury. Coactivating TLR2 reduced the injurious effects of dectin-1 activation. When injected into traumatically injured spinal cord, TLR2 agonists enhance the endogenous macrophage reaction while conferring neuroprotection. Indeed, dieback of axons was reduced, leading to smaller lesion volumes at the peak of the macrophage response. Moreover, the density of NG2+ cells expressing vimentin increased in and near lesions that were enriched with TLR2-activated macrophages. In dectin-1-null mutant (knock-out) mice, dieback of corticospinal tract axons also is reduced after SCI. Collectively, these data support the hypothesis that the ability of macrophages to create an axon growth-permissive microenvironment or cause neurotoxicity is receptor dependent and it may be possible to exploit this functional dichotomy to enhance CNS repair. SIGNIFICANCE STATEMENT: There is a growing appreciation that macrophages exert diverse functions in the injured and diseased CNS. Indeed, both macrophage-mediated repair and macrophage-mediated injury occur, and often these effector functions are elicited simultaneously. Understanding the mechanisms governing the reparative and pathological properties of activated macrophages is at the forefront of neuroscience research. In this report, using in vitro and in vivo models of relevance to traumatic spinal cord injury (SCI), new data indicate that stochastic activation of toll-like and c-type lectin receptors on macrophages causes neuroprotection or neurotoxicity, respectively. Although this manuscript focuses on SCI, these two innate immune receptor subtypes are also involved in developmental processes and become activated in macrophages that respond to various neurological diseases

Multicenter study of the impact of community-onset Clostridium difficile infection on surveillance for C. difficile infection

OBJECTIVE: To evaluate the influence of community-onset/healthcare facility-associated cases on Clostridium difficile infection (CDI) incidence and outbreak detection. DESIGN: Retrospective cohort. SETTING: Five acute-care healthcare facilities in the United States. METHODS: Positive stool C. difficile toxin assays from July 2000 through June 2006 and healthcare facility exposure information were collected. CDI cases were classified as hospital-onset (HO) if they were diagnosed > 48 hours after admission or community-onset/healthcare facility-associated if they were diagnosed ≤ 48 hours from admission and had recently been discharged from the healthcare facility. Four surveillance definitions were compared: HO cases only and HO plus community-onset/healthcare facility-associated cases diagnosed within 30 (HCFA-30), 60 (HCFA-60) and 90 (HCFA-90) days after discharge from the study hospital. Monthly CDI rates were compared. Control charts were used to identify potential CDI outbreaks. RESULTS: The HCFA-30 rate was significantly higher than the HO rate at two healthcare facilities (p<0.01). The HCFA-30 rate was not significantly different from the HCFA-60 or HCFA-90 rates at any healthcare facility. The correlations between each healthcare facility’s monthly rates of HO and HCFA-30 CDI were almost perfect (range, 0.94–0.99, p<0.001). Overall, 12 time points had a CDI rate >3 SD above the mean, including 11 by the HO definition and 9 by the HCFA-30 definition, with discordant results at 4 time points (κ = 0.794, p<0.001). CONCLUSIONS: Tracking community-onset/healthcare facility-associated cases in addition to HO cases captures significantly more CDI cases but surveillance of HO CDI alone is sufficient to detect an outbreak

Staphylococcus aureus bacteriuria as a prognosticator for outcome of Staphylococcus aureus bacteremia: a case-control study

<p>Abstract</p> <p>Background</p> <p>When <it>Staphylococcus aureus </it>is isolated in urine, it is thought to usually represent hematogenous spread. Because such spread might have special clinical significance, we evaluated predictors and outcomes of <it>S. aureus </it>bacteriuria among patients with <it>S. aureus </it>bacteremia.</p> <p>Methods</p> <p>A case-control study was performed at John H. Stroger Jr. Hospital of Cook County among adult inpatients during January 2002-December 2006. Cases and controls had positive and negative urine cultures, respectively, for <it>S. aureus</it>, within 72 hours of positive blood culture for <it>S. aureus</it>. Controls were sampled randomly in a 1:4 ratio. Univariate and multivariable logistic regression analyses were done.</p> <p>Results</p> <p>Overall, 59% of patients were African-American, 12% died, 56% of infections had community-onset infections, and 58% were infected with methicillin-susceptible <it>S. aureus </it>(MSSA). Among 61 cases and 247 controls, predictors of <it>S. aureus </it>bacteriuria on multivariate analysis were urological surgery (OR = 3.4, p = 0.06) and genitourinary infection (OR = 9.2, p = 0.002). Among patients who died, there were significantly more patients with bacteriuria than among patients who survived (39% vs. 17%; p = 0.002). In multiple Cox regression analysis, death risks in bacteremic patients were bacteriuria (hazard ratio 2.9, CI 1.4-5.9, p = 0.004), bladder catheter use (2.0, 1.0-4.0, p = 0.06), and Charlson score (1.1, 1.1-1.3, p = 0.02). Neither length of stay nor methicillin-resistant <it>Staphylococcus aureus </it>(MRSA) infection was a predictor of <it>S. aureus </it>bacteriuria or death.</p> <p>Conclusions</p> <p>Among patients with <it>S. aureus </it>bacteremia, those with <it>S. aureus </it>bacteriuria had 3-fold higher mortality than those without bacteriuria, even after adjustment for comorbidities. Bacteriuria may identify patients with more severe bacteremia, who are at risk of worse outcomes.</p

Introduction to A Compendium of Strategies to Prevent Healthcare-Associated Infections In Acute-Care Hospitals: 2022 Updates.

Since the initial publication of A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals in 2008, the prevention of healthcare-associated infections (HAIs) has continued to be a national priority. Progress in healthcare epidemiology, infection prevention, antimicrobial stewardship, and implementation science research has led to improvements in our understanding of effective strategies for HAI prevention. Despite these advances, HAIs continue to affect ∼1 of every 31 hospitalized patients, leading to substantial morbidity, mortality, and excess healthcare expenditures, and persistent gaps remain between what is recommended and what is practiced.The widespread impact of the coronavirus disease 2019 (COVID-19) pandemic on HAI outcomes in acute-care hospitals has further highlighted the essential role of infection prevention programs and the critical importance of prioritizing efforts that can be sustained even in the face of resource requirements from COVID-19 and future infectious diseases crises.The Compendium: 2022 Updates document provides acute-care hospitals with up-to-date, practical expert guidance to assist in prioritizing and implementing HAI prevention efforts. It is the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Disease Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the American Hospital Association (AHA), and The Joint Commission, with major contributions from representatives of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Pediatric Infectious Disease Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), the Surgical Infection Society (SIS), and others